crossing96/oncoscreening huggingface dataset:
A Snapshot from the Italian Clinical Practice Regarding Efficacy and Utility Rate of Perioperative Chemotherapy in Muscle-invasive Bladder Cancer: The RealBLADDER Study.	BACKGROUND/AIM: The standard of care for patients with muscle-invasive bladder cancer (MIBC) is treatment with radical cystectomy (RC) and perioperative platinum-based chemotherapy (neoadjuvant or adjuvant). Perioperative treatment can improve overall survival (OS), and the most robust evidence favors neoadjuvant chemotherapy (NAC). The RealBLADDER study assessed the efficacy and safety of perioperative chemotherapy in patients with MIBC in an Italian real-world setting. PATIENTS AND METHODS: RealBLADDER enrolled patients with MIBC treated with perioperative chemotherapy from June 2018 to June 2023. The primary endpoint was the rate of non-invasive downstaging (NID) (ypT0/pTis/pTaN0 or <ypT1N0) and complete pathological response (pCR) (yp0N0), defined as the absence of residual tumor cells in the bladder and lymph nodes at the pathological examination after NAC. Secondary endpoints were disease-free survival (DFS), OS and surgical outcomes. RESULTS: A total of 173 eligible patients were identified. One hundred and thirty-seven patients (79.2%) received NAC and 36 (20.8%) received adjuvant chemotherapy (AC). The NID rate was 36.8%, and pCR achieved in 33.6% of patients treated with NAC. The rate of surgical morbidity and mortality were 20.9% and 0%, respectively. The 12-month DFS was 73.7% [95% confidence interval (CI)=0.672-0.808]. The 12-month OS rate in the entire population was 92.1% (95%CI=0.880-0.963). Compared to AC, DFS was improved in patients treated with NAC (p=0.019). CONCLUSION: NAC is associated with an improved DFS compared to AC, a high rate of NID and pCR and low rate of surgical morbidity and mortality, supporting NAC as the preferred perioperative strategy for MIBC in clinical practice.	bladder
Dual molecular axis of resistance and immunoresponsiveness to BCG in pT1 non-muscle invasive bladder cancer: Insights from HER-2, SERBP1, HABP4, and IFN-γ profiling.	Bacillus Calmette-Guérin (BCG) immunotherapy remains the cornerstone of adjuvant treatment for high-risk non-muscle invasive bladder cancer (NMIBC); however, therapeutic failure is particularly frequent in pT1 disease, resulting in early recurrence and progression to muscle-invasive cancer. Identifying biomarkers to anticipate BCG failure is a current clinical priority to improve patient stratification and enable risk-adapted, bladder-sparing interventions. We retrospectively analyzed a cohort of 48 patients with histologically confirmed pT1 NMIBC treated with standard intravesical BCG at two tertiary centers. The median age was 67 years (range: 41-93), 79.2 % were male, 81.2 % had high-grade tumors, 70.8 % had multifocal lesions, and 75.0 % presented tumors > 3 cm. Formalin-fixed, paraffin-embedded tumor samples were obtained prior to BCG and, when available, at recurrence or progression. Immunohistochemical expression of HER-2, SERBP1, HABP4, and IFN-γ was quantified using semi-quantitative scoring and H-scores. Associations with recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated using Kaplan-Meier survival analysis and Cox regression. HER-2 and SERBP1 were significantly overexpressed in BCG-refractory tumors, with high immunorectivities conferring markedly reduced RFS (HER-2: 7.78 vs. 11.71 months, p < 0.001; SERBP1: 7.64 vs. 11.52 months, p < 0.0001) and inferior PFS (p < 0.05). In contrast, high HABP4 and IFN-γ immunorectivities were strongly associated with sustained recurrence- and progression-free survival (both p < 0.0001). Hazard ratios for recurrence and progression exceeded 5.0 for HER-2/SERBP1-high and IFN-γ/HABP4-low profiles. These findings define two molecular phenotypes-immune-evasive versus immune-active-that may inform precision risk stratification, early intervention, and personalized therapeutic decision-making in high-risk NMIBC.	bladder
A novel spatial framework to validate arsenic exposure gene expression profiling in bladder cancer using multiplex FISH and AI-powered digital pathology.	Bladder cancer exhibits marked spatial heterogeneity in gene expression and immune infiltration. In this exploratory pilot study, we integrate multiplex fluorescence in situ hybridization (mFISH) with AI-assisted digital pathology to characterize the spatial distribution of a previously validated three-gene arsenic-responsive risk model (NKIRAS2, AKTIP, HLA-DQA1). Initially identified in arsenic-exposed individuals and associated with bladder cancer risk, this gene panel achieved 94% training and 75% validation AUC in prior genomic models (PMC8760535). We analyzed five bladder tumor specimens using whole-slide mFISH imaging and HoverNet-based nuclear segmentation to quantify gene expression at single-cell resolution. Spatial profiling revealed elevated expression scores in tumor-adjacent regions, with a strong positive correlation to tumor grade (Pearson's r = 0.83). These gene-enriched regions exhibited spatial clustering of tumor cells. Additionally, tumor-infiltrating lymphocyte (TIL) density was inversely correlated with tumor grade, suggesting immune exclusion in high-grade tumors. Our findings demonstrate the feasibility of combining spatial transcriptomics with AI-driven histopathological analysis for biomarker validation. This integrative framework provides a foundation for future population-scale studies leveraging spatial omics to evaluate arsenic-associated gene signatures and assess their relevance in bladder cancer risk stratification and disease progression.	bladder
PAQR4: A Critical Senescence-Related Gene Influencing Immune Evasion and Metastasis in Bladder Urothelial Carcinoma.	Background: Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor known for its high recurrence rates and limited therapeutic efficacy. Cellular senescence has been extensively shown to inhibit tumorigenesis via cell cycle arrest. Consequently, the identification of senescence-associated biomarkers is essential for enhancing the diagnosis, prognosis, and immunotherapeutic outcomes of BLCA. Method: This study integrated the TCGA-BLCA and GSE13507 datasets to analyze senescence-related genes. ConsensusClusterPlus was employed for cluster analysis, while immune infiltration was assessed using CIBERSORT. A diagnostic and prognostic model for BLCA was developed and validated through the combination of various machine learning algorithms. Experimental validation was conducted using qRT-PCR, colony formation, and Transwell assays to evaluate the functional role of PAQR4. Result: Our study revealed that aging-related samples demonstrated improved survival rates and a lower incidence of high-grade tumors. Cluster analysis identified two distinct subgroups of BLCA characterized by unique immune infiltration profiles and varying responses to immune checkpoint blockade. The diagnostic and prognostic models developed from aging-related genes were subsequently validated. Notably, PAQR4 was identified as a critical aging-related gene linked to poor prognosis and an immunosuppressive microenvironment. The knockdown of PAQR4 significantly inhibited the proliferation and metastasis of BLCA cells. Conclusion: PAQR4 is a novel biomarker and therapeutic target for BLCA, influencing cellular senescence, immune evasion, and metastasis. This study provides insights into the senescence-related mechanisms and offers tools for precision diagnosis and the optimization of immunotherapy in BLCA.	bladder
Real-world evaluation of the efficacy and safety of disitamab vedotin (RC48) in urothelial carcinoma.	BACKGROUND: Urothelial carcinoma (UC) is an aggressive malignancy with limited options for patients unresponsive to chemotherapy or immunotherapy. Disitamab vedotin (RC48), a HER2-targeted antibody-drug conjugate(ADC), has shown promising results in clinical trials, but real-world data are lacking. METHODS: We conducted a single-center retrospective study of patients with histologically confirmed UC who received RC48 alone or in combination with PD-1 inhibitors between August 2022 and June 2024. Key inclusion criteria were at least one measurable lesion and adequate organ function; patients with incomplete records, concurrent active malignancies, or severe organ dysfunction precluding systemic therapy were excluded. RESULTS: A total of 71 patients were included. The ORR was 69.0%, including 15 complete and 34 partial responses. The median PFS was 24 months, and OS data were immature at cutoff. In subgroup analyses, patients receiving RC48 + PD-1 inhibitors achieved an ORR of 70.0% versus 63.6% with RC48 monotherapy. Grade ≥ 3 treatment-related adverse events occurred in 21.1% of patients, most commonly anemia and decreased appetite; events were generally manageable with supportive care and dose modification. CONCLUSIONS: RC48 showed encouraging activity and manageable safety in a real-world UC cohort. Prospective multicenter studies with longer follow-up are needed to validate these findings, compare monotherapy versus combination strategies, and define the optimal role of RC48 across UC disease stages.	bladder
Angiogenesis-related gene NID2 profiling and immune infiltration in bladder cancer: prognostic implications and immunotherapy response.	BACKGROUND: Immunotherapy has progressively gained prominence as a cornerstone therapeutic modality across diverse oncological contexts, with its clinical efficacy intricately linked to the dynamic interactions between the tumor microenvironment (TME) and neoplastic cells. Central to this paradigm is angiogenesis-a quintessential hallmark of cancer-which not only sustains tumor growth but also orchestrates immunomodulatory networks within the TME, thereby profoundly influencing therapeutic responsiveness. However, in the field of bladder cancer (BC), the relationship among angiogenesis and prognosis, immunotherapy response, and immune cell infiltration remains to be further explored. METHODS: To systematically uncover this relationship, we carried out an exhaustive assessment of 36 genes linked to angiogenesis (AAGs) and explored the relationship between angiogenesis and transcript, prognostic outcomes, as well as the infiltration of immune cells. By constructing an AAG_score, we quantified the angiogenic subtype characteristics of each patient. Subsequently, we evaluated the value of these characteristics in foreseeing BC prognosis and the response of treatment, and concurrently analyzed the performance of AAGs in diffuse large B-cell lymphoma for comparative study. Through RT-qPCR, CCK8 and other experiments, we verified the role of NID2 in bladder cancer. RESULTS: This study explored different types of AAGs mutations in BC samples at the genetic level and elucidated the expression patterns of AAGs. Through in-depth analysis, we identified two distinct molecular subpopulations and found significant associations between AAG mutations and patients' clinicopathological features, prognosis, and invasive TME. We found that patients with low AAG_score showed increased microsatellite instability, high mutation tendency, and immune motivation, and had a better prognosis. NID2 plays a role in promoting proliferation in bladder cancer and evaluate in diffuse large B-cell lymphoma. In addition, our study found a significant correlation between index of cancer stem cell and AAG_score in drug sensitivity. CONCLUSION: In summary, our study successfully identified prognosis-related AAG characteristics in BC patients. These characteristics not only contribute to a clearer understanding of TME properties but also provide an important basis for exploring more effective immunotherapy strategies.	bladder
[Vaginal and Vulval Secondary Extramammary Paget's Disease Associated with Urothelial Carcinoma in Situ : A Case Report].	The patient is an 80-year-old woman who initially underwent transurethral resection of a bladder tumor (TURBT) 7 years ago for bladder cancer at another hospital and was diagnosed with urothelial carcinoma (UC), high grade, pT1, followed by 8 cycles of intravesical BCG instillation therapy. Subsequently, her voiding urine cytology began to show suspicion of malignancy. When voiding urine cytology started to show positive findings, two transurethral biopsies of bladder mucosae and one selective upper tract urine cytology were performed with no evidence of malignancy, so she was followed up as an outpatient. She began experiencing spontaneous pain near the urethra and pain on urination 5 years after the initial TURBT. At this time, cystoscopy revealed redness on the posterior bladder wall. Additionally, redness of the vagina and induration of the labia were observed, raising suspicion of Paget's disease or Bowen's disease. She underwent a biopsy of the vulvar, which revealed UC. Ultimately, biopsies of the bladder, urethra, and vulvovaginal regions were performed at our hospital to determine a treatment plan. Immunohistochemical staining of the vulva was positive for cytokeratins 7 and 20 and negative for GCDFP15, confirming a diagnosis of extramammary Paget disease secondary to bladder CIS. As a result, the patient underwent radical surgery, including removal of the vagina, uterus, bladder, and labia. Pathological findings showed extensive CIS in the vagina and labia majora. Herein, we report a very rare case of secondary extramammary Paget disease extending from bladder CIS to the vagina and labia.	bladder
Combining molecular patterns and clinical data for better immune checkpoint inhibitor prediction in metastatic urothelial carcinoma.	BACKGROUND: The therapeutic landscape of advanced urothelial carcinoma (UC) is evolving, making the prediction of immune checkpoint inhibitor (ICI) therapy efficacy crucial. Standalone biomarkers offer limited predictive value, necessitating integrative approaches combining clinicopathological, laboratory, and molecular factors to enhance accuracy. This study aimed to evaluate clinical and molecular factors, including the real-life performance of PD-L1 IHC, to improve treatment outcome prediction in ICI-treated UC patients, ultimately developing a more precise therapy selection model. METHODS: We conducted a retrospective, multicenter study on advanced or metastatic UC patients with available formalin-fixed, paraffin-embedded tumor samples who underwent ICI therapy (n = 100). NanoString technology was used to analyze 770 immune-related genes and a 60-gene panel for molecular subtype classification. Identified genes were validated in the IMvigor210 dataset. Whole tissue PD-L1 expression was assessed using the Dako 22C3 antibody. RESULTS: Our findings show that PD-L1 IHC has limited predictive value for ICI response. However, among multigene molecular factors, the neuronal signature, MDA p53-like, and TCGA-luminal-infiltrated subtypes were linked to improved OS. Additionally, we identified and validated five novel ICI-predictive genes (PSMB10, HLA-E, IRF7, CXCL12, and C3), and by combining molecular and clinicopathological parameters, we developed a model with enhanced predictive value. CONCLUSIONS: Our real-life cohort analysis confirms the limitations of standalone biomarkers like PD-L1. We identified gene expression-based markers with strong prognostic and predictive value for ICI treatment outcomes.	bladder
Carbon footprint and staff demands of surgery and chemoradiation for muscle-invasive bladder cancer.	OBJECTIVE: To calculate the environmental and labour impact of two complete care pathways for patients with muscle-invasive bladder cancer (MIBC) with similar oncological outcomes: radical cystectomy (RC) and chemoradiation (CRT), by quantifying the total carbon footprint and staff demands. PATIENTS AND METHODS: The RC was robot-assisted surgery with pelvic lymph node dissection and ileal conduit. CRT included 20 fractions of 2/2.75 Gy with mitomycin C (Day 1) and capecitabine every radiation day. Waste audits identified medical products (n = 284), for which a cradle-to-gate environmental impact analysis was conducted from treatment selection to first post-treatment evaluation. Energy use was based on primary data, technical specifications or literature. Patient travel was based on the average distance, assuming petrol-fuelled cars. Staff demands were assessed by timing clinical staff assignment. The carbon footprint was calculated in CO(2)-equivalents using the Ecoinvent Database 3.10. RESULTS: The carbon footprint was 208 kg CO(2)-equivalents for RC vs 264 kg CO(2)-equivalents for CRT. The larger footprint of CRT arose from travel movements and energy use: 5- and 1.5-fold higher than RC, respectively. Main contributors to the total footprint were medical products for RC (49%), and patient travel for CRT (74%). A hotspot analysis identified 10 medical products with the highest impact, which accounted for 60% of the total impact of all medical products. RC averaged 93.5 staff hours per patient vs 29.0 staff hours per patient for CRT. CONCLUSIONS: This is the first study to analyse the environmental impact of complete care pathways in uro-oncology. Key strategies to reduce the carbon footprint of MIBC treatment include low-impact patient travel, reviewing high-impact surgical products, and using renewable energy by hospitals. Insight into staff demands per treatment assists efficient allocation of scarce personnel.	bladder
Synergistic nanoplatform of M1 macrophage-derived extracellular vesicles and MoS(2) for tumor-targeted photoimmunotherapy in bladder cancer.	Bladder cancer is among the most challenging malignancies, necessitating innovative therapeutic strategies to address tumor recurrence and progression. This study investigates the therapeutic potential of M1 macrophage-derived extracellular vesicles (M1 EVs) engineered with molybdenum disulfide (MoS(2)), forming a hybrid system (M1 EVs@MoS(2)) for combined photothermal and immunotherapy. MoS(2) nanoparticles provide excellent photothermal conversion and photocatalytic efficiency under near-infrared (NIR) irradiation, enabling precise tumor ablation and enhanced reactive oxygen species (ROS) generation. Concurrently, M1 EVs modulate the tumor microenvironment by promoting M1 macrophage polarization and enhancing antitumor immunity. Our findings demonstrate that M1 EVs@MoS(2) significantly suppresses bladder tumor growth through synergistic mechanisms: modulation of immune cytokines, robust photothermal effects, and oxidative stress induction. Immunofluorescence analysis revealed increased CD8(+) T-cell infiltration, dendritic cell activation, and reduced PD-L1 expression, indicating immune reprogramming within the tumor microenvironment. Furthermore, the biomimetic properties of M1 EVs facilitated tumor-specific delivery, minimizing off-target effects. This multifunctional platform offers a promising approach to integrate photothermal therapy with immune modulation, addressing the limitations of conventional therapies and paving the way for advanced precision oncology. Future studies will focus on optimizing formulation parameters, evaluating in vivo efficacy, and exploring combinatory treatments with immune checkpoint inhibitors.	bladder
MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells.	Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high recurrence and poor survival, accounting for the majority of bladder cancer-related deaths. A subset of MIBC harbors FGFR1 amplification or overexpression, associated with increased proliferation and poor prognosis. Although the pan-FGFR inhibitor erdafitinib has demonstrated clinical benefit in patients with FGFR3/FGFR2 alterations, primarily in non-MIBC, its efficacy is limited by resistance and toxicity. Moreover, its effectiveness in FGFR1-driven MIBC remains unclear. To address this gap, we investigated erdafitinib response and resistance mechanisms in JMSU1 cells, a model of FGFR1-amplified MIBC. While erdafitinib initially suppressed tumor growth, prolonged treatment led to resistance, characterized by persistent activation of ERK, AKT, and STAT1 signaling pathways. Mechanistic studies identified MET activation, driven by MET gene amplification, as a key driver of resistance. Notably, exogenous hepatocyte growth factor (HGF) not only induced resistance but also accelerated the emergence of MET-amplified, HGF-independent subpopulations under drug pressure. We also identified SHP2 as a critical mediator of FGFR1-driven ERK activation in parental cells. In resistant cells, MET activation enhanced SHP2-ERK signaling through the adaptor protein GAB1, reinforcing the resistant phenotype. Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy.	bladder
Red single wavelength emitting up-conversion nanoparticles modulate cellular dynamics and gene expression in T24 bladder cancer cells.	Bladder cancer persists in posing a significant global health challenge, highlighting the need for the development of advanced therapeutic strategies. This study investigates the effects of red single-wavelength upconversion nanoparticles (UCNPs), co-doped with Sm(3)⁺ and Nd(3)⁺ in a NaYbF(4) matrix, on T24 bladder cancer cells. The UCNPs were synthesized using a thermal decomposition method and characterized for their optical, structural, and morphological properties. The nanoparticles exhibited strong red emission under 980 nm near-infrared (NIR) excitation. Cytotoxicity assays revealed concentration-dependent cell death, with enhanced effects under radiation. Wound healing assays demonstrated that UCNPs reduced cellular repair mechanisms, with radiation further enhancing this effect. Gene expression analysis revealed significant modulation of key genes involved in cancer progression, including upregulation of IL-6, and downregulation of anti-apoptotic genes such as BCL2, HIF, and Survivin. Additionally, UCNPs raised the levels of reactive oxygen species (ROS), indicating oxidative stress. These findings highlight the therapeutic potential of UCNPs in bladder cancer treatment.	bladder
Shared decision-making in urinary reconstruction among radical cystectomy patients: a thematic analysis of patient and provider perspectives in China.	BACKGROUND: Shared decision-making (SDM) improves outcomes in urinary reconstruction after radical cystectomy, but its implementation in China remains understudied. This qualitative study explores SDM barriers and facilitators from patient and provider perspectives. METHODS: This study employed purposive sampling to recruit healthcare professionals and patients undergoing radical cystectomy from a single tertiary hospital. A qualitative approach involving semi-structured interviews was used to capture participants' perspectives. Thematic analysis was applied to identify key themes and subthemes. RESULTS: A total of 11 healthcare professionals and 15 patients with bladder cancer participated. Thematic analysis identified 4 main themes and 15 subthemes. (1) Decision autonomy and experience: encompassing patients' participation levels, confidence, and anxiety, and providers' attention to patient trust and preferences. (2) Information acquisition and understanding: including patients' information sources and comprehension abilities; and methods used by healthcare professionals to communicate medical information. (3) Professional expertise and occupational burden: exploring patients' perceptions of doctors' authority and skills; with role strain and emotional challenges faced by providers. (4) Social security and education: addressing gaps in health literacy; protection of patient rights; and inadequacies in SDM-related education. CONCLUSIONS: SDM in China is limited by systemic challenges, including health literacy deficits, clinician workload, and policy gaps. Targeted interventions such as patient education, communication training, and policy reforms are needed to enhance collaborative decision-making.	bladder